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Mitochondrial respiration and respiration‐associated proteins in cell lines created through Parkinson’s subject mitochondrial transfer
Author(s) -
Esteves A. Raquel,
Lu Jane,
Rodova Mariana,
Onyango Isaac,
Lezi E,
Dubinsky Richard,
Lyons Kelly E.,
Pahwa Rajesh,
Burns Jeffrey M.,
Cardoso Sandra M.,
Swerdlow Russell H.
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06631.x
Subject(s) - mitochondrion , cellular respiration , biology , respiration , cell culture , microbiology and biotechnology , cell , oxidative phosphorylation , biochemistry , genetics , anatomy
J. Neurochem. (2010) 113 , 674–682. Abstract Parkinson’s disease (PD) is associated with perturbed mitochondrial function. Studies of cytoplasmic hybrid (cybrid) cell lines containing mitochondria from PD subjects suggest complex I dysfunction in particular is a relatively upstream biochemical defect. To evaluate potential downstream consequences of PD mitochondrial dysfunction, we used a cybrid approach to model PD mitochondrial dysfunction; our cybrid cell lines were generated via transfer of PD or control subject platelet mitochondria to mtDNA‐depleted NT2 cells. To confirm our PD cybrid mitochondria did indeed differ from control cybrid mitochondria we measured complex I V max activities. Consistent with other PD cybrid reports, relative to control cybrid cell lines the PD cybrid cell line mean complex I V max activity was reduced. In this validated model, we used an oxygen electrode to characterize PD cybrid mitochondrial respiration. Although whole cell basal oxygen consumption was comparable between the PD and control cybrid groups, the proton leak was increased and maximum respiratory capacity was decreased in the PD cybrids. PD cybrids also had reduced SIRT1 phosphorylation, reduced peroxisome proliferator‐activated receptor‐γ coactivator‐1α levels, and increased NF‐kB activation. We conclude mitochondrial respiration and pathways influenced by aerobic metabolism are altered in NT2 cybrid cell lines generated through transfer of PD subject platelet mitochondria.